title: Differential effects of paclitaxel and docetaxel on gap junctions affects their cytotoxicities in transfected HeLa cells.
abstract: Gap junctions (GJs) enhance the cytotoxicity of specific cancer chemotherapeutic drugs and therefore, the inhibition of functional GJs may represent a mechanism by which the toxicity of chemotherapeutics in cancer cells can be reduced. In the present study, the effects and mechanisms of paclitaxel and docetaxel on GJ intercellular communication (GJIC) and the modulation of drug cytotoxicity were investigated in HeLa cells that were stably transfected with the connexin (Cx) 32 expression plasmid. Paclitaxel, but not docetaxel, was observed to inhibit dye‑coupling through junctional channels. Gating closure rather than the alteration of Cx32 expression or its membrane localization was responsible for the inhibitory action of paclitaxel on GJ function following short‑term exposure. The results revealed that the cytotoxicity of paclitaxel or docetaxel increased in the presence of functional GJs compared with that observed when GJIC was suppressed. In addition, paclitaxel‑induced downregulation of GJIC decreased the cytotoxicity of paclitaxel in the presence of functional GJs compared with that of docetaxel, which did not affect Cx32 channels. These observations demonstrated that the differential effects of paclitaxel and docetaxel on GJIC may affect the cytotoxicity of chemotherapeutic drugs. The present study provides a promising new approach to select antineoplastics and improve drug efficacy in carcinoma cells that form GJs.
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Tang
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Dengpan
authors.initials: D
authors.lastname: Wu
authors.forename: Suzhi
authors.initials: S
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Tao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D017629:Gap Junctions / Q000187:drug effects*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014162:Transfection; D000097002:Gap Junction beta-1 Protein
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017630:Connexins; D000077143:Docetaxel; D017239:Paclitaxel; D043823:Taxoids; D000097002:Gap Junction beta-1 Protein